New carbamoylalkyl aralkylcarbamate derivatives are fatty acid amide hydrolase inhibitors, useful e.g. for the treatment of pain, emesis, neurodegenerative diseases, cancer, allergy or inflammation

摘要

2-Amino-2-oxoethyl phenylalkylcarbamate derivatives (I) are new. Also new are certain alkyl ester and oxazolidine-dione derivative intermediates. Carbamates of formula (I) and their acid addition salts, hydrates and solvates are new. n = 1-6; A = one or more groups X, Y and/or Z; X = 1-2C alkylene (optionally substituted (os) by one or more of 1-12C alkyl, cycloalkyl or cycloalkyl-(1-6C) alkyl; Y = 1-2C alkenylene (os by one or more of 1-12C alkyl, cycloalkyl or cycloalkyl-(1-6C) alkyl; Z = 3-7C cycloalkylidene or 3-7C cycloalkylene; R1 = H, halo, OH, CN, NO2, alkyl, alkoxy, alkylthio, fluoroalkyl, fluoroalkoxy or fluoroalkylthio; R2 = as R1; or phenyl, naphthyl, biphenylyl, phenylethenyl, naphthylethenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, indanyl, indenyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, phthalzinyl, cinnolinyl, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, thiadiazolyl, oxadiazolyl, triazolyl, benzothienyl, benzofuranyl, dibenzofuranyl, benzimidazolyl, benzotriazolyl, indolyl, isoindolyl, indazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, dihydroindolyl, pyrrolopyridinyl, thienopyridinyl, furopyridinyl, imidazopyridinyl, oxazolopyridinyl, thiazolopyridinyl, pyrazolopyridinyl, isoxazolopyridinyl, isothiazolopyridinyl, tetrahydroquinolinyl, isotetrahydroquinolinyl, phenoxy, phenylthio, phenylsulfonyl, benzoyl, phenylmethoxy, phenylethoxy, naphthylmethoxy, naphthylethoxy, naphthylpropoxy, quinolinyloxy or isoquinolinyl (all os by one or more of halo, CN, NO2, 1-4C alkyl, 1-4C alkoxy, 1-4C alkylthio, fluoroalkyl, fluoroalkoxy, fluoroalkylthio, phenoxy, benzyloxy, piperidinyl, pyrrolidinyl, morpholinyl, NR6R7, NHCOR6, COR6COOR6, SO2R6, 1-3C alkylenedioxy or piperazino (os by alkyl or benzyl); R6, R7 = alkyl or phenyl; R3 = -CHR4-CO-NHR5; R4 = H or alkyl; and R5 = H, alkyl, 3-5C cycloalkyl or cycloalkyl-(1-6C) alkyl; Unless specified otherwise, alkyl moieties have 1-3C and cycloalkyl moieties 3-7C. Independent claims are also included for: (1) Preparation of (I); and (2) New intermediates comprising: (a) ester compounds (I'), of formula as for (I) but having R3 replaced by -CHR4-COOR; (b) trifluoromethanesulfonated ester compounds (I''), of formula as for (I) but having R3 replaced by -CHR4-COOR and R2 replaced by R8; (c) oxazoline-diones of formula (V); and (d) trifluoromethanesulfonated oxazoline-diones (V'), of formula as for (V) but having R3 = -CHR4-COOR and R2 replaced by R8. R = Me or Et; and R8 = triflate.